Type 2 diabetes mellitus poses major health burdens for individuals, families, and populations. Particular populations appear to be especially vulnerable to type 2 diabetes (T2DM). Among these is the Mexican American population that bears a disproportionate burden of T2DM. This has doubled in the last 2 decades, and is likely to increase further with rapid population growth and aging of this relatively young population, and earlier onset of T2DM. There will be increasingly costly and debilitating consequences of complications of Type 2 diabetes in larger numbers of patients, and earlier in life than we have seen hitherto. While susceptibility to type 2 diabetes mellitus has long been known to have a substantial genetic component, we hypothesize that there are also genetic components of the various complications. Risk factors for these implications will also encompass a range of behavioral and life style components which are at presently ill-defined. Our existing program examines not only the genetic component, but also life style and socioeconomic factors associated with T2DM in the Hispanic population in a small cohort. These studies are currently limited by an insufficiently large population of participants who can be followed both for the evolution of their diabetes, as well as the complications arising as disease progresses. In particular we wish to expand our understanding beyond some of the social and behavioral components of disease progress, and in particular assess the contribution of anxiety and depression, which is little studied in Mexican Americans. To this end, we propose to expand the existing funded and approved cohort study we have established among the Mexican American population in the Lower Rio Grande Valley. We now have access to the sophisticated genome scanning studies which have proceeded rapidly and the human gene expression map is maturing. Our strategy is therefore to exploit the interaction of genomics with behavioral, socioeconomic and lifestyle measures to provide the most robust measures of the components which predispose and lead to T2DM and its complications. The identification of precise risk factors for T2DM and ts complications in a Mexican American cultural/gene interaction setting will be the most productive way to move from general to individual approaches to prevention of both disease and its many complications.